Hyposalivation and the Human Oral Microbiome

描述（由申请人提供）：唾液过少或唾液流速异常低是与冠面和根面龋齿相关的主要健康问题，尽管有最佳临床实践，但仍会严重降低生活质量。药物是慢性唾液分泌不足的最常见原因。慢性少涎的第二个主要原因是干燥综合征，这是发达国家最普遍的自身免疫性疾病之一。暴露牙齿表面的微生物群在龋齿形成中起着关键作用。为了减轻这些人群的龋齿和牙齿脱落负担，我们建议确定与急性和慢性唾液分泌不足状态以及随后的龋齿发展相关的微生物群组成的变化。检测微生物群的早期诊断变化将有助于早期治疗干预。虽然许多基于培养的研究已经研究了唾液分泌减少对口腔微生物群落的影响，但没有一项研究随着时间的推移在不同的龈上部位产生空间上明确的影响。此外，培养提供了细菌多样性和群落结构的有限视图。我们的初步，测序为基础的数据表明，龈上菌斑的分类组成不同的牙齿之间和在缺唾液。这一发现，结合观察到龋齿的分布以特定的方式转移到切牙和犬齿的状态下的hyposalivation，表明我们需要检查时空变化的龈上社区的存在和不存在hyposalivation，如果我们要了解（并最终防止）的进展，从健康相关hyposalivation和龋齿相关的社区状态。本申请通过定义和表征健康中以及急性和慢性唾液分泌不足状态下多个空间和时间尺度上龈上微生物群落的群体水平转变和差异来解决这一需求。目的1：在没有唾液分泌不足的情况下，表征健康成人龈上和唾液微生物群的时空动态。目的2：表征药物诱导的唾液减少对健康成人龈上和唾液微生物群的急性影响。目的3：评估慢性少涎对干燥综合征患者龈上和唾液微生物群的影响。我们的长期目标是开发新的诊断标志物，用于低唾液相关的致龋微生物群落，以及开发新的基于生态的治疗方法，以降低高危患者的龋齿发病率，并更好地了解微生物群落在致龋中的作用。

DESCRIPTION (provided by applicant): Hyposalivation, or an abnormally low salivary flow rate, is a major health problem associated with coronal and root surface dental caries, and a profound reduction in quality of life despite best clinical practices. Medications are the most common cause of chronic hyposalivation. A second major cause of chronic hyposalivation is Sj�gren's Syndrome, one of the most prevalent autoimmune disorders in the developed world. The microbiota of the exposed tooth surface plays a critical role in caries formation. In order to reduce the burden of caries and tooth loss in these populations, we propose to identify shifts in the composition of the microbiota that are associated with the acute and chronic states of hyposalivation and the subsequent development of caries. Detection of early diagnostic changes in the microbiota will facilitate early therapeutic intervention. Although many culture-based studies have examined the impact of hyposalivation on oral microbial communities, none have examined spatially explicit impacts at distinct supragingival sites over time. Furthermore, cultivation provides a limited view of bacterial diversity and community structure. Our preliminary, sequencing-based data show that the taxonomic composition of supragingival plaques varies between and across teeth in the absence of hyposalivation. This finding, combined with the observation that the distribution of caries shifts in a site-specific manner to the incisors and canines in states of hyposalivation, suggests that we need to examine spatiotemporal variation in supragingival communities in the absence and presence of hyposalivation if we are to understand (and ultimately prevent) the progression from health- associated to hyposalivation- and caries-associated community states. This Application addresses this need by defining and characterizing population-level transitions and differences in supragingival microbial communities at multiple spatial and temporal scales in health and in acute and chronic states of hyposalivation. Aim 1: Characterize the spatiotemporal dynamics of the supragingival and salivary microbiota in healthy adults in the absence of hyposalivation. Aim 2: Characterize acute impacts of medication-induced hyposalivation on the supragingival and salivary microbiota of healthy adults. Aim 3: Evaluate impact of chronic hyposalivation on the supragingival and salivary microbiota in patients with Sj�gren's Syndrome. Our long-term objectives are to develop new diagnostic markers for hyposalivation-associated cariogenic microbial communities, as well as to develop novel ecologically-based therapeutics to decrease dental caries incidence in high risk patients, and to understand better the role of microbial communities in cariogenesis.